Arrowhead Presents Overview of Its Broad RNAi Delivery Platform and Introduces New Subcutaneously Administered Format

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Arrowhead Presents Overview of...

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical

company developing targeted RNAi therapeutics, today presented an

overview of its broad RNAi delivery platform at the Annual Meeting of

the Oligonucleotide Therapeutics Society in Leiden, the Netherlands.

Included in this presentation was data from a new program, ARC-LPA,

which is designed to reduce production of apolipoprotein A [apo(a)], a

key component of lipoprotein(a) [Lp(a)]. Lp(a) has been genetically

linked with increased risk of cardiovascular diseases, independent of

cholesterol and LDL levels. Using a new subcutaneous delivery construct

that Arrowhead has developed, an initial lead compound has achieved up

to 90% knockdown of apo(a) in mice.

“Our ability to generate RNAi drugs for a wide variety of indications

has expanded dramatically with our advances in delivery,” said Chris

Anzalone, Ph.D., Arrowhead’s president and chief executive officer. “We

currently have two drugs in the clinic, ARC-520 and ARC-AAT, that

validate our capabilities in IV liver delivery and provide additional

confidence in follow-on candidates ARC-F12 and ARC-521. We are now able

to deliver to tumors, as exemplified by ARC-HIF2, and report data today

on subcutaneous administration for liver delivery with ARC-LPA. These

capabilities provide broad opportunities to fight diverse diseases and

enable us to drive an aggressive pipeline.”

In a presentation titled, “Development of RNAi-Based Therapeutics

using Dynamic Polyconjugates™ (DPC™) Technology,” Bruce Given, M.D.,

Arrowhead’s chief operating officer, discussed three examples of

Arrowhead’s broad RNAi delivery platform: DPC™ for liver delivery with

select data from the ARC-520 clinical program; DPC™ for extra-hepatic

delivery with select preclinical data from the ARC-HIF2 program; and, a

new proprietary subcutaneous delivery vehicle with initial preclinical

data from the ARC-LPA program.

Arrowhead uses DPC™, or Dynamic Polyconjugates™, for liver delivery in

both of its clinical stage drugs, ARC-520 for chronic hepatitis B

infection and ARC-AAT for alpha-1 antitrypsin deficiency, as well as

additional preclinical stage programs, including ARC-F12 for hereditary

angioedema and ARC-521 for chronic hepatitis B infection. Arrowhead’s

delivery platform can produce deep and sustained knockdown of mRNA and

proteins, as evidenced by data from the ARC-520 program showing dramatic

reductions in hepatitis B e-antigen, core-related antigen, and s-antigen

in humans. ARC-520 achieved a maximum reduction of s-antigen of 99% (1.9

log), which is the highest reported single-dose knockdown in humans with

any RNAi therapeutic.

DPC™ for extra-hepatic delivery is being deployed in Arrowhead’s

ARC-HIF2 candidate for the treatment of clear cell renal cell carcinoma

(ccRCC). As Arrowhead previously reported, in an orthotopic ccRCC tumor

model in mice ARC-HIF2 reduced the expression of HIF2α, a well-validated

oncogene in this disease, by more than 80%, leading to statistically

significant reductions in tumor size and weight, extensive tumor cell

death, reduction in the tumor-expressed VEGF-A biomarker, and

destruction of the blood vessels feeding the tumors. DPC™ for

extra-hepatic delivery employs a masked polymer designed to induce

endosomal escape, with RNAi trigger attached directly to the delivery

vehicle. This molecule is actively guided to tumor cells with a

proprietary targeting agent that binds to αVβ3 integrin, which is highly

expressed on the surface of ccRCC cells as well as various other tumor

types.

Dr. Given also introduced Arrowhead’s new hepatic delivery format being

developed for subcutaneous administration and a new target being

explored for cardiovascular disease. The new delivery construct

discussed includes an RNAi trigger against apo(a). Apo(a) is a critical

component of Lp(a) and effective knockdown results in marked Lp(a)

reductions. Single dose knockdown of around 90% in apo(a) has been

achieved in mice. Initial data through day 15 suggest a good duration of

effect (study ongoing). Similar to the intravenously administered

vehicle used for hepatic delivery, this construct employs N-acetyl

galactosamine for hepatic targeting. However, it does not employ the

same peptide-based active endosomal escape. An active lead compound has

been identified and additional lead optimization is ongoing. This

program has not been officially designated as entering pre-IND

development.

A copy of the presentation can be accessed by visiting the Events

section of the company’s website at http://ir.arrowheadresearch.com/events.cfm

after the presentation concludes.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a biopharmaceutical company developing

targeted RNAi therapeutics. The company is leveraging its proprietary

Dynamic Polyconjugate™ delivery platform to develop targeted

drugs based on the RNA interference mechanism that efficiently silences

disease-causing genes. Arrowhead’s pipeline includes ARC-520 and ARC-521

for chronic hepatitis B virus, ARC-AAT for liver disease associated with

Alpha-1 antitrypsin deficiency, ARC-F12 for hereditary angioedema and

thromboembolic diseases, and ARC-HIF2 for renal cell carcinoma.

For more information please visit http://www.arrowheadresearch.com,

or follow us on Twitter @ArrowRes.

To be added to the Company’s email list and receive news directly,

please visit

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Safe Harbor Statement under the Private Securities Litigation Reform

Act:

This news release contains forward-looking statements within the

meaning of the “safe harbor” provisions of the Private Securities

Litigation Reform Act of 1995. These statements are based upon our

current expectations and speak only as of the date hereof. Our actual

results may differ materially and adversely from those expressed in any

forward-looking statements as a result of various factors and

uncertainties, including our ability to finance our operations, the

future success of our scientific studies, our ability to successfully

develop drug candidates, the timing for starting and completing clinical

trials, rapid technological change in our markets, and the enforcement

of our intellectual property rights. Arrowhead Research Corporation’s

most recent Annual Report on Form 10-K and subsequent Quarterly Reports

on Form 10-Q discuss some of the important risk factors that may affect

our business, results of operations and financial condition. We assume

no obligation to update or revise forward-looking statements to reflect

new events or circumstances.

DYNAMIC POLYCONJUGATES is a trademark of Arrowhead Research

Corporation.

Source: Arrowhead Research Corporation

Arrowhead Research Corporation
Vince Anzalone, CFA
626-304-3400
ir@arrowres.com
or
Investor

Relations:
The Trout Group
Chad Rubin, 646-378-2947
ir@arrowres.com
or
Media:
Russo

Partners
Matt Middleman, M.D.
212-845-4272
matt.middleman@russopartnersllc.com

Source: Arrowhead Research Corporation

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